Pathogenesis of E. coli and Shigella infections in human enteroid models
人肠模型中大肠杆菌和志贺氏菌感染的发病机制
基本信息
- 批准号:10745560
- 负责人:
- 金额:$ 12.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationAddressAttentionAttenuated VaccinesBiological Response ModifiersCell CommunicationCell modelCell physiologyCellsCellular biologyChildhoodClinicalCoculture TechniquesCollaborationsCommunicable DiseasesCulture MediaDendritic CellsDevelopmentDiarrheaDiarrheagenic E. coliDiseaseElectronic MailEnteralEnterotoxinsEnvironmentEpitheliumEscherichia coliExposure toFunctional disorderFundingGastroenterologyGlycoproteinsGoalsGoblet CellsHumanHuman ResourcesImmuneImmune EvasionImmune systemImmunologyInternationalIntestinesLaboratoriesLeukocytesM cellMacrophageMarylandMeasurementMethodologyMethodsMicrobiologyModelingMolecularMucinsMucous MembraneOrganismPathogenesisPeptide HydrolasesPhagocytesPhysiologyPorosityProductionProgram Research Project GrantsPublicationsReagentRecording of previous eventsResearchResearch PersonnelResearch Project GrantsRoleSerine ProteaseShigellaShigella InfectionsShigella VaccinesSystemT-LymphocyteTelephoneUniversitiesVirginiaWorkantimicrobial peptidecell motilitycytokinediarrheal diseaseeVisitenteric pathogenenteroaggregative Escherichia colienterotoxigenic Escherichia coliexperiencegut inflammationhuman modelimprovedinsightintraepithelialmeetingsmonolayerneutrophilnovelpathogenpathogenic bacteriapre-clinicalprogramsresponsescaffoldshear stresstooltranscytosis
项目摘要
Pathogenesis of E. coli and Shigella Infections in Human Enteroid Models
Overall Description / Summary
This first renewal of a funded program Project Grant (PPG) is to continue progress in understanding the
pathophysiology and identification of ways to interfere with diarrhea caused by Shigella and two pathotypes of
diarrheagenic E. coli (enteroaggregative and enterotoxigenic E. coli). The substantial progress made has
resulted from the close collaboration and combined expertise of investigators from the University of Maryland,
Johns Hopkins University and the University of Virginia who are using shared models of normal human enteroid
and colonoid monolayers exposed to enteric bacterial pathogens as well as human enteroid monolayers co-
cultured with innate phagocytic cells present in the intestine. The group of investigators has internationally
renowned experience in enteric diseases, as well as in microbiology, gastroenterology, molecular physiology,
pediatric infectious diseases, cell biology, molecular pathogenesis, and mucosal immunology. This consortium
has interacted and in a superbly collaborative manner sharing technical and scientific information through formal
monthly face-to-face or Zoom-based meetings, frequent telephone or electronic communication and visits to
laboratories, with the latter being the standard form of interaction of the U Maryland and JHU investigators. The
Enteroid and Immunology Cores have developed new tools and methods that were rapidly transferred to the
Project investigators, resulting in a significant number of collaborative publications from the PPG. As expected,
progress was stepwise with transfer of methodology and reagents for propagating the enteroids, production of
monolayers, development of the bacterial-enteroid models, and development of co-cultures with immune cells
leading to new insights in the pathogen-enteroid interactions. The overall goal of the PPG remains to increase
understanding of the pathophysiology and potential treatments of these three important pathogens. The
proposed studies will continue to use normal human enteroids or colonoids, grown on monolayers, and extend
this through co-culture to make the model more closely resemble human intestine. This will be accomplished by
expanding the co-culture models to a) establish monolayers in a 3D scaffold matrix to facilitate epithelial-immune
cell interaction and immune cell movement; b) incorporate macrophages, neutrophils and dendritic cells as well
as to develop a new co-culture system that includes intraepithelial γδ +T lymphocytes (IEL); c) apply an enriched
M cell model; d) expose the co-culture model to flow-based shear stress as occurs normally in the intestine; e)
determine the contribution of an anaerobic environment. As during the past funding period, examination of
pathophysiologic aspects common to the diseases studied will serve to integrate the projects. In addition to
pathogen specific pathophysiologic aspects, these include the role of mucins, bacterial proteases called
SPATES, enterotoxins, secreted cytokines and involvement of co-cultured innate immune cells.
大肠杆菌和志贺氏菌感染在人肠道模型中的发病机制
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Protocol for measuring transcytosis and recycling of IgG in intestinal epithelial Caco-2 cells and primary human intestinal organoids.
- DOI:10.1016/j.xpro.2023.102335
- 发表时间:2023-05-25
- 期刊:
- 影响因子:0
- 作者:Maeda, Keiko;Gwilt, Katlynn Bugda;Schmieder, Stefanie S.;Zachos, Nicholas C.;Lencer, Wayne I.
- 通讯作者:Lencer, Wayne I.
Co-culturing Human Intestinal Enteroid Monolayers with Innate Immune Cells.
人肠肠样单层细胞与先天免疫细胞共培养。
- DOI:10.1007/978-1-0716-3076-1_16
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Staab,JanetF;Lemme-Dumit,JoseM;Latanich,Rachel;Pasetti,MarcelaF;Zachos,NicholasC
- 通讯作者:Zachos,NicholasC
Human Breast Milk Enhances Intestinal Mucosal Barrier Function and Innate Immunity in a Healthy Pediatric Human Enteroid Model.
- DOI:10.3389/fcell.2021.685171
- 发表时间:2021
- 期刊:
- 影响因子:5.5
- 作者:Noel G;In JG;Lemme-Dumit JM;DeVine LR;Cole RN;Guerrerio AL;Campbell JD;Kovbasnjuk O;Pasetti MF
- 通讯作者:Pasetti MF
Highly-conserved regulatory activity of the ANR family in the virulence of diarrheagenic bacteria through interaction with master and global regulators.
- DOI:10.1038/s41598-023-33997-0
- 发表时间:2023-04-29
- 期刊:
- 影响因子:4.6
- 作者:
- 通讯作者:
The role of the minor colonization factor CS14 in adherence to intestinal cell models by geographically diverse ETEC isolates.
- DOI:10.1128/msphere.00302-23
- 发表时间:2023-10-24
- 期刊:
- 影响因子:4.8
- 作者:Smith, Emily M.;Papadimas, Antonia;Gabor, Caitlin;Cooney, Ceanna;Wu, Tao;Rasko, David;Barry, Eileen M.
- 通讯作者:Barry, Eileen M.
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MARK DONOWITZ其他文献
MARK DONOWITZ的其他文献
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{{ truncateString('MARK DONOWITZ', 18)}}的其他基金
Mechanisms and Correction of Abnormal Bicarbonate Secretion by DRA in Diarrhea
DRA 治疗腹泻时碳酸氢盐异常分泌的机制及纠正
- 批准号:
9753444 - 财政年份:2019
- 资助金额:
$ 12.94万 - 项目类别:
Translational Approaches to Develop Drug Therapy for Diarrhea
开发腹泻药物治疗的转化方法
- 批准号:
9892562 - 财政年份:2019
- 资助金额:
$ 12.94万 - 项目类别:
Mechanisms and Correction of Abnormal Bicarbonate Secretion by DRA in Diarrhea
DRA 治疗腹泻时碳酸氢盐异常分泌的机制及纠正
- 批准号:
9981963 - 财政年份:2019
- 资助金额:
$ 12.94万 - 项目类别:
Pathogenesis of E. coli and Shigella infections in human enteroid models
人肠模型中大肠杆菌和志贺氏菌感染的发病机制
- 批准号:
10190298 - 财政年份:2016
- 资助金额:
$ 12.94万 - 项目类别:
Pathogenesis of E. coli and Shigella infections in human enteroid models
人肠模型中大肠杆菌和志贺氏菌感染的发病机制
- 批准号:
9982173 - 财政年份:2016
- 资助金额:
$ 12.94万 - 项目类别:
Pathogenesis of E. coli and Shigella infections in human enteroid models
人肠模型中大肠杆菌和志贺氏菌感染的发病机制
- 批准号:
10427388 - 财政年份:2016
- 资助金额:
$ 12.94万 - 项目类别:
Translational Approaches to Develop Drug Therapy for Diarrhea
开发腹泻药物治疗的转化方法
- 批准号:
9298626 - 财政年份:2014
- 资助金额:
$ 12.94万 - 项目类别:
Translational Approaches to Develop Drug Therapy for Diarrhea
开发腹泻药物治疗的转化方法
- 批准号:
8769280 - 财政年份:2014
- 资助金额:
$ 12.94万 - 项目类别:
Human Intestinal Organoids: Pre-Clinical Models of Non-Inflammatory Diarrhea
人类肠道类器官:非炎症性腹泻的临床前模型
- 批准号:
8668192 - 财政年份:2012
- 资助金额:
$ 12.94万 - 项目类别:
Human Intestinal Organoids: Pre-Clinical Models of Non-Inflammatory Diarrhea
人类肠道类器官:非炎症性腹泻的临床前模型
- 批准号:
8516141 - 财政年份:2012
- 资助金额:
$ 12.94万 - 项目类别:
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